I'm really only familiar with D&D 4e. Could someone give me a rundown of the major things that would be different if I were to DM Pathfinder? (I gather it is more similar to 3.5e, but I only know that from video games.)

Not interested in subjective "what is best", but rather how does it change the game mechanics (and hence DM's role) -- for example, I gather it isn't as "battle grid" oriented (a big difference). Do folks use miniatures with it? If my group were to switch to it, what would the biggest changes be?

Considering the existence of detailed answers on 'Differences between D&D 3.5 and Pathfinder', I'm not sure it is fair to call it an identical question. The answer to an amalgamated question would need to list all the features of 4e and all the features of Pathfinder/3.5 that weren't identical, so the reader could see each point of divergence and how each version did it differently. Somehow I feel this would be a very long document.
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AnanisaptaSep 3 '12 at 12:48

4 Answers
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I'm very familiar with 3.5, somewhat familiar with PF, but only know the core ruleset of 4e. Nevertheless, since no one else has answered, I thought I might as well take a stab at the major differences. I'd say the general theme is that PF offers more paths while building a character, at the cost of offering more dead ends as well. Similarly, monsters are more flexible, but more difficult for the DM to run.

I think you could write an interesting essay talking more about the philosophical and design differences between the two systems, but in answering this question it'll be more useful to address the observable differences point by point.

Class and monster roles

Fourth edition (4e) has clearly defined class and monster roles. This isn't the case at all in Pathfinder (PF). A fighter in PF might be good at dealing damage (striker) or a great tank (defender) but this will depend entirely on how you build your character. Monsters do not provide an obvious indication of how they should be used; the DM has to examine their abilities and think about what their role should be in battle.

It's very easy to build an ineffective character in PF, as a consequence of the greater flexibility you have in defining your role.

Multiclassing

Since in PF each class defines its own progression, every time a PC gains a level they can choose what class to advance in. Again, this means it is possible to design a character that performs very poorly. It would be a bit like creating a 4e character that drew from multiple classes, but was capable of using only heroic level powers while everyone else was choosing a paragon path.

Paths vs. Prestige Classes

In 4e, there are three distinct tiers of play, and you can choose a paragon path and epic destiny as you progress.

There's no direct analogue to the tiers in PF. The closest thing to a paragon path is a prestige class -- a class that can only be taken when you meet certain requirements. This was more of a big deal in 3.5, where it was used for character customization; in PF there are many fewer prestige classes, though they might be important for certain multiclass combinations.

Defenses v. Saves

This is purely technical, but confusing if you're not expecting it. Defenses in 4e are equivalent to saving throws in PF. If a wizard casts a spell, rather than rolling an attack, the defender rolls a saving throw against a DC set by the spell.

Automatic progressions

In 4e, you add half your level to a great many statistics. PF is not quite so straightforward -- your class(es) will determine your base attack bonus and saving throw progression, and you must pick how your skills improve every level. Other abilities like AC or initiative do not naturally increase as you level.

Powers, Spells, and Maneuvers

This is probably the most fundamental difference from a player's perspective.

In 4e, every class has a list of powers they can learn as they level. These powers are divided into at-will, daily, and encounter powers that dictate how often they can be used. Pretty much any special ability a player has is derived from a power -- and those powers are chiefly geared towards combat. Casting classes can gain rituals which are less combat related, and work off a different economy than combat powers.

In Pathfinder, it works a little differently. Casting classes have spells, which are probably closest in spirit to 4e powers, but tend to be more flexible. The number of spells you can choose from is quite large, and different classes have different mechanics for learning and casting these spells. Spells useful in combat consume exactly the same resources as more role-playing oriented spells.

Meanwhile, melee classes rarely have the same type of limited powers. Anyone can push, grab, pull, grapple, trip or disarm a foe during combat, and you can do so as often as you like. Doing so means sacrificing damage, though; you will only do damage with a regular attack. Unlike 4e, forced movement is quite difficult to pull off in PF, which is why a grid isn't as necessary.

As an example, a fighter in PF progresses chiefly because they get better at what they've been capable of doing all along, rather than getting spectacular new powers.

Monsters

This is a big difference from the DM's POV especially.

In addition to fitting certain roles (as mentioned above) monsters in 4e are often defined by a set of bespoke abilities. In contrast, monsters in PF always play by the same rules as the players. Their hp, attacks, saves, and skills are defined and limited by the type and HD of the monster. The majority of unique special abilities are copies of spells, or one of a small set of abilities common to many monsters. Often a powerful monster will have a large set of abilities they will never use in combat, but can provide role playing hooks.

There is no PF equivalent to elite or solo monsters -- you simply must use a higher level beast to provide a greater challenge to the party.

Overall the 4e system is much easier on the DM in creating encounters. For those so inclined, though, the PF system allows the creation of some interesting beasts; you can even add class levels to monsters, much like PCs can multiclass.

Magic items

The majority of magic items in PF do one of two things -- they either increase the attributes of a PC, or they can replicate the effects of spells. Magic weapons and armor combine several different attributes, almost Diablo style. Compared to the 4e items in core, they are much more varied, and what specific item your character has can drastically affect what they can do. The downside is that it becomes harder for a player to choose the 'correct' gear.

There's a couple of things you might want to mention - some Pathfinder monsters (such as dragons) make for very effective 'solo' encounters, whereas others (such as kobolds) are best in hordes, and some spells d orequire the caster to make an attack roll. Still, this is a very good answer, though. +1.
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GMJoeJul 24 '13 at 7:32

4e is an well-structured miniatures game with very light role-playing elements

Pathfinder (PF) is a reasonably structured combat system with far more role-playing elements

There's a blogger on the D&D forums named The Jester who has some good high-level insights:

4e is designed for you to play a fantasy action hero going through a dungeon with tactical combat encounters.

I like to think (as he often does), that roleplaying has three key elements:

Combat

Skills checks / obstacles / exploration

PC / NPC interactions

4e has a very fleshed out combat system (#1). But it's very limited on #2 & #3. Most players have few or no skills b/c doing so puts them behind on combat. 4e has the concept of "Rituals" for overcoming obstacles, but their designed means rituals aren't useful on a combat time scale: e.g., the rites for closing a portal or magically opening a door require 10+ minutes; are you really planning to sit around for 60 combat rounds waiting to close the portal after the escaping villain?

Pathfinder has much more in the way of #2 & #3. Many of the spells in the book have nothing to do with combat. Players get points for skills at each level (without spending feats), so most PCs have at least one useful non-combat skill. However, the combat in Pathfinder is much less fleshed out and balanced.

Where 4e is a boxing match, PF can be a wild west gun-slinging event. Where 4e has a large variety of balanced, tactical combat abilities, PF typically comes down to a couple of dozen combat spells and a handful of combat tricks.

In 4e, it's very easy to build a balanced combat character. In PF, a character is built out of lots of little +1s that are sometimes found in non-obvious places.

Do folks use miniatures with it?

You definitely do. The rules for moving around the grid are still well-defined. The only big adjustment is that everything is measured in 5ft squares instead of spaces representing 5ft squares.

Also, flying is accessible relatively early (about level 7 of 20), so it's nice to have some plastic tubes around for indicating height.

Could someone give me a rundown of the major things that would be different if I were to DM Pathfinder?

I think @starwed has covered a lot of the technical differences.

From a gameplay perspective I find the big difference to be "openness". In PF, games move from a "dungeon crawl" towards a "swords and spells and politics" game. You still plan encounters and try to balance out combat. But you really have to willing to roll with the punches and let the dice tell the story.

To give a concrete example. My PF party escaped a snowstorm and walked right into a Yeti cave. In 4e, that moment means that everyone rolls initiative and we take out the yetis or die trying. In PF, we don't go straight to initiative. Instead, our undead tiefling warlock jumps at them and starts yelling like a madman, rolls a 19 on his Intimidate check and they cower away from us. To ensure they don't stab us in the back over night, the other magic users cast "Speak Language" and "Charm" and convince the yetis that we won't attack them and we're not worth eating.

There's still die rolling and checks, but there's a lot more back and forth on what's possible and DM judgment calls on what's allowed. You will be reading spells details and going "can it work that way"?

I won't say that "Most players have few or no skills b/c doing so puts them behind on combat." in 4e, because you get skills based on your class and not on your intelligence score. Raising intelligence at the expense of other abilities could put someone "behind in combat" much more in PF. (also, 4e combat is as automatic as in your example only if you want it, even if it's true, diplomacy and intimidate are no more auto-win buttons)
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ZachielJul 24 '13 at 12:02

I did not start playing RPGs until D&D 4e so I have no lingering bias from earlier releases. Over the past year I have played a lot of both 4e and Pathfinder. I like them both, but they are different.

Materials:
Personally, I like the 4e books better. The pages are brighter and easier to read and I feel they explain the details more clearly. I would say they are written more for someone that has never played RPGs before. Pathfinder has great artwork, but sometimes things can be hard to find because they are described in a section you would not have thought to look in or they used italics instead of bold and the text gets lost on the page. Most of this really comes down to personal preference and how familiar you are with RPG games.

System:
Being both d20 RPGs, the games are very similar. I like both. I have played great adventures in both. The difference is in the details. 4e is much more streamlined than Pathfinder. I would not say one is better, it is more what are you looking for? Do you want a character that you can create relatively quickly that has lots of cool abilities (4e) or do you enjoy spending 2 hours researching all of the assorted options and assembling them just right (Pathfinder)? Either way is fine. It comes down to the number of options you like when creating a character.

Role Playing:
I have a different opinion when I hear that there is a lack of role playing in 4e. I disagree. The example given in a prior post was running into a Yeti cave. There is nothing in 4e that says you have to role initiative as soon as you see the yetis. 4e has an Intimidate skill just like Pathfinder. There is no reason that the characters could not do the same thing in both games. The role playing to me is a function of the game being run and who is playing more than the mechanics of the game.

I do agree that Pathfinder has more spells that can be used during role-playing, but 4e has a fair number as well. Any action that the players want to take can be broken down into a skill check, even if that check is just against Wisdom and not a true skill. I have played 4e games with a lot of role playing and skill checks and I have played Pathfinder that is combat after combat.

Combat:
So let's talk combat. This definitely where camps can get divided. While you can do a good amount of role playing in 4e, it definitely is combat-heavy. Every character gets powers or abilities or spells that let them do cool things during combat. This is a feature of the game that a lot of people like.
In Pathfinder, if you are not a class that can cast spells, then generally you are limited to bashing with your sword or firing an arrow. Some people say combat in Pathfinder is boring as a result. Some say they like that the different classes have more distinct roles in Pathfinder. Do you want characters to always have cool tricks they can perform during battles (4e) or are you more interested in the strategy of combat (Pathfinder)? Personal preference.

Skill Challenges:
I include this because it is a sensitive topic when comparing the systems. I am not crazy about skill challenges. They seem too contrived where you are forcing people to just role a certain number of skill checks instead of just letting the encounter end when the problem is solved. People will often use Skill Challenges as an argument against 4e, but despite my dislike of them, I think that is unfair. Nothing in 4e says you have to use Skill Challenges as written and I have seen plenty of encounters in Pathfinder that are essentially Skill Challenges in everything but name.

So the bottom line to me comes down to 2 questions.
1) How experienced are you with RPGs?
2) How much detail do you want?

If you have no experience and are looking for a really fun game where you can have cool characters doing awesome things (think superhero movie), then you should be happy with 4e.

If you are already familiar with RPGs and/or you want something that you can immerse yourself in like a good book and build characters with a lot of depth (think drama/action movie), then Pathfinder is probably right up your alley.

+1 "There is nothing in 4e that says you have to role initiative as soon as you see the yetis... There is no reason that the characters could not do the same thing in both games." — Very much agree.
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detlyJul 24 '13 at 1:26

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The difference I found between the 4e and Pathfinder/3.5e books (and the system they're describing) is that for a beginner to learn or even understand anything about Pathfinder/3.5e, they paradoxically already have to be practically an expert at the system. It's a learning style Catch 22. Most things don't make sense and everything just steadily begins making sense the more you learn. 4e as a system is designed and expressed in such a way that most of the system can be easily understood from the beginning - you don't need to be an expert to understand the basics.
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doppelgreenerJul 24 '13 at 2:34